We are studying the regulation of expression of the immunoglobulin gene family by attempting to answer two questions: (1) Why do only cells of the B-lymphoid line-age synthesize immunoglobulins, (2) how do these cells transcribe only one or a few immunoglobulin genes, while leaving hundreds of other, similar immunoglobulin genes inactive? Our approach to these questions is to insert cloned immunoglobulin genes into plasmids in various configurations, to transfect the plasmids into various types of cells, and to determine whether the transfected gene is transcribed. We have shown that a kappa immunoglobulin gene is transcribed after transfection into antibody-producing myeloma cells but not in non-lymphoid 3T3 or L cells. Hence the different cell types are able to appropriately regulate the kappa gene even when not in its usual chromosomal environment. By deleting different parts of the cloned gene, we have shown that an enhancer element down-stream of the promoter is necessary for its transcription in myeloma cells. We have also demonstrated that both the enhancer and the promoter are cell-type specific, that is, they function in lymphoid cells but not in non-lymphoid cells. Recently, we have observed that the kappa enhancer stimulates the kappa promoter 20-fold more than it stimulates other promoters. This synergism between the kappa enhancer and promoter suggests the existence of a protein that binds to both regulatory elements.